DESCRIPTION: This grant application investigates the nature of anti-viral host immune responses against papillomaviruses, specifically cottontail rabbit papillomavirus ( CRPV). Specifically, the PI describes experiments to investigate whether CRPV infection leads to a modulation of expression of CD40 in rabbit keratinocytes. This T-lymphocyte co-stimulatory molecules has recently been detected in human keratinocytes. Therefore the PI hypothesizes that modulation of its expression by papillomavirus infection could alter host immune responses. The three aims of this grant are 1) to clone the rabbit homologue of CD40, 2) to establish whether rabbit CD40 is expressed in rabbit keratinocytes, and 3) to determine whether its expression is present in tissue infected with CRPV and whether this expression differs in those lesions that represent persistent infections, or progressing versus regressing lesions.